長期連續性的濫用藥物、環境線索引發藥物渴求進而導致藥癮復發等，都說明藥癮記憶在藥物使用上扮演一個特殊關鍵的角色。與藥物連結的記憶在近來的研究也被認為是藥癮之所以難以戒除的原因。直至今日，對於藥癮記憶提取過程之相關機制依然不甚了解。然而，杏仁核一向被認為是與調節情緒經驗的儲存及情感記憶相關的神經核，另外前額葉也同時被證實在連結式學習的關鍵。 然而先前的研究指出蛋白質合成為古柯鹼造成的場地偏好中所必需。所以我們利用藥物學的方式，試圖從三條以往被證實參與在長期記憶形成的細胞分子途徑-分別包含PKC，MEK/ERK及PKA/cAMP，找出何者與古柯鹼記憶有關。 其中使用H89 (為選擇性的磷酸激脢A抑制劑)去干擾PKA/cAMP途徑；U0126為MEK激脢抑制劑；NPC15437則為磷酸激脢C抑制劑。所以本研究目的在於利用上述藥物去研究在杏仁核(側底核)及前額葉中，找出究竟哪些分子途徑其下游牽涉的蛋白質合成，才是參與古柯鹼相關記憶中提取和再穩固化歷程。

Continuous drug use, context-induced drug craving, and relapse all manifest the critical roles of specific memory episodes associated with the drug use experiences. Memory for the drug-associated cues have been reported to resist extinction and contribute to the drug relapse; To date, little is known about the molecular mechanisms underlying the retrieval and reconsolidation of such drug memory. Amygdaloid complex has been known for its physiological function in mediating emotional experience storage and emotional cue-regulated memory retrieval. Otherwise the medial prefrontal cortex have also been shown to be critical for learning in both aversive and appetitive settings. This study was undertaken to determine the relevance of several intracellular signaling molecular pathways in basolateral amygdala and medial prefrontal cortex, known for their involvement in various kinds of long-term memory, to the cue-elicited cocaine memory retrieval and reconsolidation. Previously, we demonstrated that the protein synthesis was necessary for the retrieval of cocaine-induced place preference memory. We proposed to use pharmacological methods to study the roles of PKC, MEK/ERK, and PKA/cAMP pathways in amygdala and prefrontal cortex to find out which signaling pathways were responsible for retrieval and reconsolidation of cocaine-associated memory. In this study, we use H89, a selective inhibitor of PKA, to inhibit the activation of PKA to interfere PKA/cAMP pathway. U0126 is an inhibitor of ERK kinase MEK, which has been known to decrease the phosphorylation level of CREB and NPC 15437, a PKC inhibitor. Therefore we’ve used pharmacological methods to establish the possible molecular mechanisms of retrieval and reconsolidation in drug-associated memory.

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